Category Archives: 2018

2018, Publicación, Renal

Gutierrez et al. Eur J Med Chem. 2018;157:946-959. Discovery of potent calpain inhibitors based on the azolo-imidazolidenone.

Publications > Gutierrez et al

Eur J Med Chem. 2018, 157, 946 PubMed 30165342

Discovery of potent calpain inhibitors based on the azolo-imidazolidenone.

Sara Gutierrez1, Maria Moron1, Mercedes Griera2, David Sucunza1, Laura Calleros2, Andrea Garcia-Jerez2, Claire Coderch3, Francisco J Hermoso3, Carolina Burgos1, Manuel Rodriguez-Puyol2, Beatriz de Pascual-Teresa3, Maria L Diez-Marques2, Antonio Jimenez2, Miguel Toro-Londono2, Diego Rodriguez-Puyol4, Juan J Vaquero1

1. Departamento de Quimica Organica y Quimica Inorganica, Universidad de Alcala.  2. Departamento de Biologia de Sistemas, Universidad de Alcala, 28871, Alcala de.  3. Departamento de Quimica y Bioquimica, Facultad de Farmacia, Universidad San.  4. Research Unit and Nephrology Section, Hospital Principe de Asturias and.

Keywords: Azolo-imidazolidenone; Blockade of apoptosis; Calpain inhibitors; SAR; Uncompetitive inhibition

Abstract

A series of new azolopyrimidine-peptide hybrids and indolomethylideneimidazolones

2018, AzaBN, Publicación

Abengozar et al. Org Lett. 2018;20(16):4902-4906. C-H Functionalization of BN-Aromatics Promoted by Addition of Organolithium Compounds to the Boron Atom.

Publications > Abengozar et al

Org Lett. 2018, 20, 4902 PubMed 30070487

C-H Functionalization of BN-Aromatics Promoted by Addition of Organolithium Compounds to the Boron Atom.

Alberto Abengozar1, Miguel Angel Fernandez-Gonzalez2, David Sucunza1, Luis Manuel Frutos2, Antonio Salgado3, Patricia Garcia-Garcia1, Juan J Vaquero1

1. Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala , 28805 Alcala de Henares , Madrid , Spain.  2. Departamento de Quimica Analitica, Quimica Fisica e Ingenieria Quimica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala , 28805 Alcala de Henares , Madrid , Spain.  3. Centro de Espectroscopia de Resonancia Magnetica Nuclear (CERMN), CAI Quimicas , Universidad de Alcala , 28805 Alcala de Henares , Madrid , Spain.

Abstract

Addition of an organolithium compound to a BN-phenanthrene with embedded B and N atoms is proposed to result in coordination of RLi to the boron atom. This coordination, supported by NMR spectroscopy and DFT calculations, increases the nucleophilicity of the system in the beta position to the N atom and is therefore a useful tool for promoting regioselective C-H functionalization of BN aromatics.

2018, Publicación, TosMIC

Gutierrez et al. J Org Chem. 2018;83(12):6623-6632. gamma-Carboline Synthesis by Heterocyclization of TosMIC Derivatives.

Publications > Gutierrez et al

J Org Chem. 2018, 83, 6623 PubMed 29756452

gamma-Carboline Synthesis by Heterocyclization of TosMIC Derivatives.

Sara Gutierrez, David Sucunza, Juan J Vaquero

Departamento de Quimica Organica y Quimica Inorganica and Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala , 28805 - Alcala de Henares , Madrid , Spain.

Abstract

A new method for the synthesis of gamma-carbolines by a heterocyclization that involves alpha-indol-2-ylmethyl TosMIC derivatives and different electrophiles has been developed. This methodology has been successfully applied to the synthesis of several highly substituted gamma-carbolines.

2018, Publicación

Malvicini et al. Mol Cancer Ther. 2018;17(5):966-976. A Tricin Derivative from Deschampsia antarctica Desv. Inhibits Colorectal Carcinoma Growth and Liver Metastasis through the Induction of a Specific Immune Response.

Publications > Malvicini et al

Mol Cancer Ther. 2018 May;17(5):966-976. doi: 10.1158/1535-7163.MCT-17-0193. Epub 2018 Feb 26. PubMed 29483221

A Tricin Derivative from Deschampsia antarctica Desv. Inhibits Colorectal Carcinoma Growth and Liver Metastasis through the Induction of a Specific Immune Response.

Mariana Malvicini1, Ana Gutierrez-Moraga2, Marcelo M Rodriguez3, Sofia Gomez-Bustillo1, Lorena Salazar1, Carlos Sunkel2, Leonor Nozal2, Antonio Salgado4, Manuel Hidalgo4, Pedro P Lopez-Casas5, Jose Luis Novella6, Juan Jose Vaquero4, Julio Alvarez-Builla4, Adda Mora4, Manuel Gidekel7, Guillermo Mazzolini2, a

1. Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomedicas, CONICET- Universidad Austral, Buenos Aires, Argentina.  2. Universidad Autonoma de Chile, Providencia, Chile.  3. Universidad de La Frontera, Temuco, Chile.  4. Departamento de Quimica Organica, Universidad de Alcala, Madrid, Spain.  5. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.  6. Gastrointestinal Cancer Clinical Research Unit, CNIO - Spanish National Cancer Research Center, Madrid, Spain.  7. Creative BioScience, Huechuraba, Santiago, Chile.

a. gmazzoli@cas.austral.edu.ar, mgidekel@creativebio-science.com

Abstract

In colorectal carcinoma patients, distant metastatic disease is present at initial diagnosis in nearly 25% of them. The majority of patients with metastatic colorectal carcinoma have incurable disease; therefore, new therapies are needed. Agents derived from medicinal plants have already demonstrated therapeutic activities in human cancer cells. Antartina is an antitumor agent isolated from Deschampsia antarctica Desv. This study aimed to evaluate the antitumor properties of Antartina in colorectal carcinoma models. We used human and murine colorectal carcinoma cell lines for investigating proliferation, apoptosis, and cell-cycle effects of Antartina therapy in vitro Avatar and immunocompetent colorectal carcinoma animal models were applied for evaluating the effects of Antartina in vivo Immune response against colorectal carcinoma model was investigated using CTL assay, analyzing dendritic cell activation and intratumor T-cell subpopulation, and by tumor rechallenge experiments. Antartina inhibits in vitro human colorectal carcinoma cell proliferation; however, in vivo experiments in Avatar colorectal carcinoma model Antartina display a limited antitumor effect. In an immunocompetent colorectal carcinoma mice model, Antartina potently inhibited tumor growth and liver metastases, leading to complete tumor regressions in >30% of mice and increased animal survival. In addition, Antartina induced a potent specific cytotoxic T-cell response against colorectal carcinoma and a long-lasting antitumor immunity. Interestingly, Antartina increased tumor immunogenicity and stimulated dendritic cell activation. No toxic effects were observed at the doses employed. Our findings showed that Antartina has the ability to induce antitumor immunity against colorectal carcinoma and can be used to develop new tools for the treatment of colorectal carcinoma. Mol Cancer Ther; 17(5); 966-76. (c)2018 AACR.

2018, BioImag, Publicación

Bosch et al. Org. Chem. Front.. 2018;5(12):1916-1927. Dibenzopyridoimidazocinnolinium cations: a new family of light-up fluorescent DNA probes.

Publications > Bosch et al

Org. Chem. Front. 2018, 5, 1916

Dibenzopyridoimidazocinnolinium cations: a new family of light-up fluorescent DNA probes.

Pedro Bosch1, David Sucunza1, Francisco Mendicuti2, Alberto Domingo3, Juan J Vaquero1

1. Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala , 28805 Alcala de Henares , Spain.  2. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Spain.  3. Departamento de Biología de Sistemas, Universidad de Alcalá, Spain.

Abstract

Steady-state and time-resolved fluorescence, circular dichroism and molecular modelling techniques have been applied to a new family of weakly fluorescent dibenzopyridoimidazocinnolinium derivatives whose fluorescence intensity increases significantly (larger than × 3.5) upon DNA addition. The synthesis of these azonia cations, which bind to DNA by intercalation, was carried out using a Westphal condensation and a Suzuki cross coupling reaction as key steps. A live-cell staining analysis by confocal microscopy imaging was also performed and showed the capacity of these new compounds for active uptake and accumulation by living cells, with complex patterns of intracellular distribution observed.

2018, AzaBN, Publicación

Abengozar et al. Chem Commun (Camb). 2018;54(20):2467-2470. Synthesis of functionalized helical BN-benzo[c]phenanthrenes.

Publications > Abengozar et al

Chem Commun 2018, 54, 2467 PubMed 29319090

Synthesis of functionalized helical BN-benzo[c]phenanthrenes.

Alberto Abengozara, Patricia Garcia-Garcia, David Sucunza, Adrian Perez-Redondo, Juan J Vaquero

Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR), Universidad de Alcala, 28805-Alcala de Henares, Madrid, Spain.

a. patricia.garciagarci@uah.es, juanjose.vaquero@uah.es

Abstract

A novel parent BN-benzo[c]phenanthrene, with helical chirality and remarkable structural features, has been easily obtained in three steps with a global yield of 55%. Moreover, Cl-substituted derivatives have been prepared and these have served as useful starting materials for the development of palladium-catalyzed cross-coupling reactions.